Haloperidol receptor blockade

Haloperidol Blockade of D2 receptors >> 5HT2A receptors Some a blockade, but minimal M receptor blockade and much less sedation than the phenothiazines Schizophrenia (alleviates positive symptoms), bipolar disorder (manic phase), Huntington s chorea, Tourette s syndrome Oral and parenteral forms with metabolism-dependent elimination Toxicity Extrapyramidal dysfunction is major adverse effect... 

Parkinsonian adverse effects occur more commonly with haloperidol than with thioridazine. One possible explanation is that thioridazine exerts more pronounced blocking actions at brain muscarinic receptors. This action partly compensates for dopamine receptor blockade in the ni-grostriatal tract, so that extrapyramidal function is more effectively maintained. A second possibility (not listed) is that haloperidol has a higher affinity for dopamine D2 receptors than does thioridazine. The answer is (D). 

Hauber (1996) examined the effects of dopamine D1 or D2 receptor blockade on initiation and execution of movements using a simple reaction time task for rats. The preferential D2 antagonist haloperidol caused a delayed movement initiation, as indicated by an inrease in reaction time. In addition, movement execution was slowed. He concluded that D1 and D2 receptors are both involved in movement initiation and execution processes. 

The answer is b. (Hardman, pp 282—283J Central dopamine receptors are divided into Dt and D2 receptors. Antipsychotic activity is better correlated to blockade of D2 receptors. Haloperidol, a potent antipsychotic, selectively antagonizes at Dz receptors. Phenothiazine derivatives, such as chlorpromazine, fluphenazine, and promethazine, are not selective for D2 receptors. Bromocriptine, a selective D2 agonist, is useful in the treatment of parkinsonism and hyperprolactinemia. It produces fewer adverse reactions than do nonselective dopamine receptor agonists... 

The answer is d. (Hardman, pp 407-4122) Haloperidol is a butyro phenone derivative with the same mechanism of action as the phe-nothiazines, that is, blockade of dopaminergic receptors. It is more selective for D2 receptors. Haloperidol is more potent on a weight basis than the phenothiazines, but produces a higher incidence of extrapyra-midal reactions than does chlorpromazine. 

Because of multiple receptor actions, which occur at different concentrations, different neuroleptics have different action profiles. There are many classifications for neuroleptic drugs, the least useful of which is probably based on their chemical structure. Other classifications include linear classifications based on the propensity to cause EPS, or multidimensional ones such as the Liege star which combines information on three positive effects (anti-autistic, antiproductive, antipsychotic), and three negative (hypotensive, extrapyramidal, sedative). In a general way, the more sedative neuroleptics such as levomepromazine, used more to treat acute agitation states, cause more hypotension related to alpha blockade, whereas those that act best on delirium (productive states) such as haloperidol tend to cause more EPS. 

The chronic injection of haloperidol, but not clozapine, increases selectively the concentration of enkephalins in the striatum. Protracted blockade of dopamine receptors by haloperidol causes a reduction in nigral content of substance P-like immunoreactivity, and of substance P and substance K mRNAs. Moreover, the effects of haloperidol on substance P is nonuniform in various areas of brain. 

Secondary parkinsonism Parkinsonian symptoms infrequently follow viral encephalitis or multiple small vascular lesions. Drugs such as the phenothiazines and haloperidol (see p. 127), whose major pharmacologic action is blockade of dopamine receptors in the brain, may also produce parkinsonian symptoms. These drugs should not be used in parkinsonian patients. 

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